chrX-153648240-A-C

Position:

• chrX-153648240-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001318503.2(DUSP9):​c.287A>C​(p.Glu96Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.000016 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: DUSP9 NM_001318503.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.412

Genes affected

DUSP9 (HGNC:3076): (dual specificity phosphatase 9) The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which is associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product shows selectivity for members of the ERK family of MAP kinases and is localized to the cytoplasm and nucleus. Aberrant expression of this gene is associated with type 2 diabetes and cancer progression in several cell types. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.123681396).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DUSP9	NM_001318503.2	c.287A>C	p.Glu96Ala	missense_variant	2/4	ENST00000342782.4
DUSP9	NM_001395.4	c.287A>C	p.Glu96Ala	missense_variant	2/4
DUSP9	XM_011531123.2	c.380A>C	p.Glu127Ala	missense_variant	2/4
DUSP9	XM_047441899.1	c.353A>C	p.Glu118Ala	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DUSP9	ENST00000342782.4	c.287A>C	p.Glu96Ala	missense_variant	2/4	1	NM_001318503.2	P1
DUSP9	ENST00000370167.8	c.287A>C	p.Glu96Ala	missense_variant	2/4	1		P1

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000164 AC: 16 AN: 975616 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 307026

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000229

Gnomad4 NFE exome AF: 0.0000141

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 24

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 09, 2022

The c.287A>C (p.E96A) alteration is located in exon 2 (coding exon 1) of the DUSP9 gene. This alteration results from a A to C substitution at nucleotide position 287, causing the glutamic acid (E) at amino acid position 96 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.065
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	17
DANN	Benign	0.75
DEOGEN2	Benign	0.066	T;T
FATHMM_MKL	Benign	0.20	N
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	0.10	N;N
REVEL	Benign	0.029
Sift	Benign	0.70	T;T
Sift4G	Benign	0.66	T;T
Polyphen		0.24	B;B
Vest4		0.11
MutPred		0.37		Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);
MVP		0.79
MPC		0.55
ClinPred		0.12	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6
Varity_R		0.095
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152913694;